​Due to major advances in our understanding of cancer, new drugs are now being designed to specifically target the "Achille's Heel" of tumour cells in order to improve treatment responses and reduce the burden of treatment-related side effects.

However, it is essential to ensure that the pathway (or ‘Achille’s heel’) to be targeted is essential to the growth and survival of a tumour before resources are committed to drug development programmes. This process is known as 'validating the drug target'.

What target is this research trying to validate?

Dr Sarah Welsh and Dr Sandra Strauss are investigating the role of hypoxia, determining if this area may highlight the ‘Achilles Heel’ of bone cancer and validate a new drug target. Hypoxia is a period of low oxygen levels in cells and a molecule known as HIF-1α is responsible for helping cells to survive this period. However, extended periods of hypoxia usually result in the body signalling to kill the affected cells.

HIF1α can offer a survival benefit to tumour cells, which exploit and express the molecule in higher amounts than normal cells; allowing tumour cells to survive and the tumour to progress. Its expression is increased in many human tumours, including osteosarcoma and chondrosarcoma, but is absent in most normal tissues - making HIF-1α an attractive target for the development of new cancer drugs.

This research project aimed to validate HIF-1α as a legitimate drug target in various forms of primary bone cancer; primarily osteosarcoma and chondrosarcoma. Previous studies have shown that inhibiting the function of HIF-1α leads to an effect on other molecules in the cells to ultimately lead to an inhibition of growth and survival in sarcoma cells. Moving this forward, this study took a closer look at HIF1α inhibition, using a novel inhibitor of HIF1α known as CL67, to extend the previously published results.

What did this study find and what are the next steps for this work?

Results of this study demonstrate that HIF-1α inhibition by CL67 leads to inhibition of sarcoma cell growth and ability to form colonies. This work has therefore validated HIF-1α as a potential therapeutic target in sarcoma and CL67 as a novel anticancer agent warranting further investigating in future studies.

This project was funded in 2010

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